Whilst the reactions of the citric acid cycle [l] and related pathways are well established, the manner in which the flux through the pathway is regulated in different tissues remains an area of active research and debate. The primary focus during the last decade has been on enzyme mechanisms, the intracellular compartmentation of enzymes and intermediates of the cycle, and on the interrelations with the specific anion translocating systems of the inner mitochondrial membrane. A number of recent reviews have been concerned with relating citric acid cycle activity to the regulation of carbohydrate and fatty acid oxidation [2-41, metabolite transport across the mitochondrial membrane for gluconeogenesis, ureogenesis and fatty acid synthesis [5-l 11, cellular energy metabolism [12-l 61, as well as with more specialized topics such as pyruvate [17,181 and ethanol [191 metabolism. The concept that the enzymes of the citric acid cycle are organized as a functional multienzyme complex has also been advocated [20, 21]. Until recently it has been generally’accepted that turnover of the citric acid cycle per se is regulated at the dehydrogenase level primarily by the mitochondrial NAD’/NADH ratio. This ratio is linked to the* mitochondrial ATP/ADP ratio and ultimately to the cytosolic phosphorylation potential, which is a primary factor in the control of tissue respiration. However, since the different NAD’substrate dehydrogenases are regulated with different sensitivities by the NAD’INADH ratio, the absolute NAD’redox potential for a given flux depends on the concentration and nature of the substrate supply to the mitochondria. On the other hand, the anaplerotic functions of the citric acid cycle are regulated by ancillary enzymes such as pyruvate dehydrogenase, pyruvate